Drug products: Lukasm, Montegen, Montelukast 2care4, Montelukast Accord, Montelukast Actavis, Montelukast Bluefish, Montelukast Ebb, Montelukast Krka, Montelukast Mylan, Montelukast Navamedic, Montelukast Orion, Montelukast Ranbaxy, Montelukast Sandoz, Montelukast STADA, Montelukast Teva, Singulair, Singulair®, Singulair-AR®
ATC code: R03DC03
Substances: montelukast, montelukast sodium
No sex differences in effect or safety of montelukast have been observed in adults. Studies in children with asthma have shown contradictory results on differences in the effect of montelukast.
In our opinion, the present evidence does not motivate differentiation in dosing or treatment between men and women.
Some studies suggest that there are sex differences in expression and diagnosing of asthma, and it has been discussed if women/girls are under-treated for respiratory diseases or not [1, 2].
According to studies conducted by the manufacturer, no sex differences in pharmacokinetics have been identified for montelukast [3, 4].
There is also a published study of pharmacokinetics of i.v. and oral montelukast where healthy adult volunteers (9 men, 9 women) participated in a double-blind, placebo-controlled single rising dose study. There were no differences in the absorption or distribution of montelukast between men and women .
Studies shows conflicting findings whether there are sex differences in the effect of montelukast in children with asthma.
A randomized, double-blind, placebo-controlled, multinational study evaluated montelukast (4 mg once daily) in 2-5-year-old children with asthma (404 boys, 285 girls). The improvement of montelukast on asthma control was consistent across age, sex and race . Another randomized, placebo-controlled trial evaluated the effect of adding montelukast (4-5 mg once daily) to current asthma therapy in children 2-14 years old with asthma (127 boys, 67 girls). Study outcome was number of days with worse asthma symptoms. Boys had greater benefit from montelukast in the younger ages (2-5 years), whereas girls had greater benefit in older ages (10-14 years) .
Increased levels of urinary leukotriene E4 (LTE4) has been associated with loss of asthma control. The effect of montelukast on cysteinyl leukotrienes (CysLTs) was investigated in a placebo-controlled study including children aged 6-15 years (19 boys, 9 girls). Increased LTE4 declined with montelukast treatment and was greater in girls than boys (p=0.07) .
In adults, similar response to add-on montelukast (10 mg once daily) was observed in men and women in a subgroup analysis of a prospective open-label study (1097 men, 567 women). Efficacy was measured with total Asthma Control Score and Mini-Asthma Quality-of-life Questionnaire .
A large cohort study (520 men, 680 women) investigated the impact of sex and age on response to asthma therapy (including salbutamol, salmeterol, inhaled budesonide, zafirlukast, montelukast, beclomethasone and inhaled corticosteroids). There was no difference between men and women in treatment failure for any individual therapy. Individuals aged 30 years and older were more likely to have treatment failure but the risk was similar for men and women .
An analysis of spontaneously reported psychiatric adverse drug reactions in children in Sweden during 2001-2010, showed that suicidality was more reported in boys and associated with treatment with several drugs of different drug-classes among them montelukast .
The growth effect of asthma treatment in children below 5 years of age was investigated in a retrospective cohort study. The children were treated with beclomethasone (38 boys, 24 girls), fluticasone (23 boys, 9 girls) or oral montelukast (38 boys, 13 girls) for at least 6 months. The three treatment groups had similar effect on growth rates. Girls had a slower growth than boys .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
The effect of montelukast on future risk of myocardial infarction and ischemic stroke was examined in a Swedish nationwide population-based cohort study between 2005-2008 (31447 men and 49 909 women). Post hoc analyses showed no association between montelukast use and patients’ sex for incident myocardial infarction, incident stroke or recurrent stroke. For recurrent myocardial infarction, montelukast was associated with a higher risk in women but not in men (HR 0.65, p=0.046) .
A retrospective cohort study from the U.S. showed that boys were more likely than girls to fill a prescription for montelukast for allergic rhinitis (OR 1.17). There was no sex difference among adults .
Date of litterature search: 2017-05-28
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson